CONJUGATION OF BENZOIC-ACID WITH GLYCINE IN THE HUMAN FETAL AND ADULTLIVER AND KIDNEY

The rate of hippuric acid formation was measured in the homogenates ob tained from 26 specimens of human adult liver, 9 specimens of human mi d-gestational fetal liver, 5 specimens of human adult kidney and 11 sp ecimens of human mid-gestational fetal kidney. The average (pmol/min/m g tissue +/- SD) rate of hippuric acid formation was 322 +/- 99 (adult liver), 7.6 +/- 3.6 (fetal liver), 284 +/- 117 (adult kidney) and 6.4 +/- 6.7 (fetal kidney). One third of the fetal livers and kidneys stu died were inactive in the formation of hippuric acid. These findings i ndicate that the conjugation of carboxylic acid with glycine is poorly developed in the mid-gestational human fetus. The kinetics of the for mation of hippuric acid were studied in 3 fetal and adult livers and a lso in 3 fetal kidneys and in 3 specimens of the cortex and medulla of adult kidneys. The transformation of the data into Eadie-Hofstee plot s generated straight lines in fetal and adult livers and kidneys. The Michaelis-Menten constant for the formation of hippuric acid (mean +/- SD, mM) was 43.4 +/- 6.6 (adult liver), 27.3 +/- 10.1 (fetal liver), 33.3 +/- 6.1 (adult renal cortex), 34.7 +/- 11.3 (adult renal medulla) and 15.3 +/- 3.5 (fetal kidney). The maximum velocity of the reaction (mean +/- SD, pmol/min/mg tissue) was 204 +/- 47.8 (adult liver), 6.0 +/- 1.3 (fetal liver), 199 +/- 40.7 (adult renal cortex), 24.2 +/- 16 .9 (adult renal medulla) and 6.4 +/- 1.8 (fetal kidney). The inhibitor y effect of 8 drugs containing a carboxylic acid group on the rate of hippuric acid formation was studied in 3 adult livers. Salicylic acid and diflunisal were the most powerful as inhibitors. Ibuprofen, furose mide and sodium valproate were weak inhibitors, whereas ketoprofen, na proxen and captopril did not inhibit the formation of hippuric acid. T he IC50 values (mean +/- SD) of salicylic acid and diflunisal on the r ate of hippuric acid formation were 0.19 +/- 0.05 and 1.1 8 +/- 0.19 m M, respectively.